Clinical Functional Magnetic Resonance Imaging Research Articles

Effect of bone marrow aspiration concentrate and platelet-rich plasma combination in anterior cruciate ligament reconstruction: a randomized, prospective, double-blinded study

BackgroundThe effect of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) combination in enhancing graft maturation and tendon–bone tunnel interfacial healing after anterior cruciate ligament (ACL) reconstruction remains unclear. We hypothesised that BMAC and PRP combination could lead to better clinical results and better graft maturation/interface healing than PRP alone or conventional ACL reconstruction without any other biologic augmentation.MethodsIn this randomised double-blind prospective study, patients undergoing ACL reconstruction surgery were randomly assigned into three groups: (1) control group (without any biologic augmentation), (2) PRP treatment group, and (3) combined BMAC and PRP (BMAC + PRP) group. Moreover, they were evaluated using the clinical functional score, laxity examination, and magnetic resonance imaging (MRI) analysis.ResultsNo significant difference was observed in the improvement of functional scores among groups. However, laxity improvement at 24 weeks showed a significant difference with the BMAC + PRP group having the lowest laxity. MRI analysis showed no significant change in whole graft maturation among groups. In particular, the BMAC + PRP group showed delayed signal peak and higher graft signal at 24 weeks compared with the other two groups; however, the difference was not significant. With regard to tendon–bone interfacial healing, the BMAC + PRP group showed significantly wider tendon–bone interface in the femoral bone tunnel at 24 weeks compared with the other two groups. Moreover, the BMAC + PRP group showed significantly higher peri-tunnel edema signal in the femoral bone tunnel at 12 weeks compared with the other two groups.ConclusionPRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon–bone interfacial healing compared with control (no additional treatment). When BMAC is used in ACL reconstruction, the possibility of greater inflammation in the early stage to graft maturation and bone tunnel healing should be considered.

The Duration of Chronic Pain Can Affect Brain Functional Changes of the Pain Matrix in Patients with Chronic Back Pain: A Resting-State fMRI Study.

This study was conducted to explore the differences in functional changes in the pain matrix in patients with chronic back pain (CBP) at different stages and identify whether these brain changes were related to the pain duration. In this study, 29 healthy individuals and 54 patients with CBP were recruited. According to the pain duration, 25 patients (3 to 12 months) were divided into the CBP-S group and 29 patients (≥ 24 months) were divided into the CBP-L group. All subjects completed clinical pain-related measurement and functional magnetic resonance imaging (fMRI) scans. Moreover, the amplitude of low-frequency fluctuation (ALFF), functional connectivity (FC), and correlation analysis were conducted in this study. Compared with healthy controls, patients in the CBP-L group showed significantly decreased ALFF in the left precuneus. In the FC analysis, patients in the CBP-S and CBP-L groups showed significantly decreased FC in several regions in the bilateral orbitofrontal cortices (OFC) and the left ventral posterior insula. Moreover, there were significant differences in the FC between the left hyper granular insula and the probabilistic area in OFC in pairwise group comparisons. The correlation analysis results demonstrated that pain duration was correlated with these functional brain changes, and the ANCOVA results revealed that pain intensity and pain interference scores did not affect the FC analysis results. There are different changes in the pain neural matrix in patients with chronic pain at different stages. Furthermore, the pain duration is related to brain functional changes.

Cognitive inflexibility is linked to abnormal frontoparietal-related activation and connectivity in obsessive-compulsive disorder.

Although it was acknowledged that patients with obsessive-compulsive disorder (OCD) would exhibit cognitive inflexibility, the underlying neural mechanism has not been fully clarified. Therefore, this study aimed to investigate the neural substrates involved in cognitive inflexibility among individuals with OCD. A total of 42 patients with OCD and 48 healthy controls (HCs) completed clinical assessment and functional magnetic resonance imaging (fMRI) data collection during cued task switching. Behavioral performances and fMRI activation were compared between the OCD group and the HC group. Psychophysiological interactions (PPIs) analyses were applied to explore functional connectivity related to task switching. Pearson correlation was used to investigate the relationships among behavioral performance, fMRI activity, and obsessive-compulsive symptoms in OCD. The OCD group had a greater switch cost than HCs (χ2 = 5.89, p < .05). A significant difference in reaction time was found during switch (χ2 = 17.72, p < .001) and repeat (χ2 = 16.60, p = .018) between the two groups, while there was no significant difference in group accuracy. Comparison of group differences showed that the OCD group had increased activation in the right superior parietal cortex (rSPL) during task switching, and exhibited increased connectivity of frontoparietal network/default mode network (FPN-DMN; i.e., middle frontal gyrus [MFG]/inferior parietal cortex-precuneus, MFG-middle/posterior cingulate gyrus) and within the FPN (inferior parietal cortex-postcentral gyrus). In the OCD group, the compulsion score was positively correlated with accuracy during switch (r = .405, p = .008, FDRq <.05), and negatively correlated with activation of rSPL (r = -.328, p = .034, FDRq >.05). Patients with OCD had impaired cognitive flexibility and cautious response strategy. The neural mechanism of cognitive inflexibility in OCD may involve increased activation in the rSPL, as well as hyperconnectivity within the FPN and between the FPN and DMN.

Altered resting-state cerebellar-cerebral functional connectivity in patients with panic disorder before and after treatment

The study aimed to investigate the functional connectivity (FC) between the cerebellum and intrinsic cerebral networks in patients with panic disorder (PD), and to observe changes in the cerebellar-cerebral FC following pharmacotherapy. Fifty-four patients with PD and 54 healthy controls (HCs) underwent clinical assessments and functional magnetic resonance imaging scans before and after a 5-week paroxetine treatment. Seed-based cerebellar-cerebral FC was compared between the PD and HC groups, as well as between patients with PD before and after treatment. Additionally, the correlations between FC and clinical features of PD were analyzed. Compared to HCs, patients with PD had altered cerebellar-cerebral FC in the default mode, affective-limbic, and sensorimotor networks. Moreover, a negative correlation between cerebellar-insula disconnection and the severity of depressive symptoms in patients with PD (Pearson correlation, r = −0.424, p = 0.001, Bonferroni corrected) was found. After treatment, most of the enhanced FCs observed in patients with PD at baseline returned to levels similar to those observed in HCs. However, the reduced FC at baseline did not significantly change after treatment. The findings suggest that patients with PD have specific deficits in resting-state cerebellar-cerebral FC and that paroxetine may improve PD by restoring the balance of cerebellar-cerebral FC. These findings emphasize the crucial involvement of cerebellar-cerebral FC in the neuropsychological mechanisms underlying PD and in the potential pharmacological mechanisms of paroxetine for treating PD.

The Registry for Migraine (REFORM) study: methodology, demographics, and baseline clinical characteristics

BackgroundErenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population.MethodsThe REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP.ResultsThe study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications.ConclusionThe REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article.Trial registrationThe study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020).

Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study

BackgroundEmerging evidence suggests that the DOCK4 gene increases susceptibility to schizophrenia. However, no study has hitherto repeated this association in Chinese, and further investigated the relationship between DOCK4 and clinical symptoms in schizophrenic patients using clinical scales and functional magnetic resonance imaging (fMRI). MethodsIn this study, we genotyped three single nucleotide polymorphisms (SNPs) (rs2074127, rs2217262, and rs2074130) within the DOCK4 gene using a case-control design (including 1289 healthy controls and 1351 patients with schizophrenia). 55 first-episode schizophrenia (FES) patients and 59 healthy participants were divided by the genotypes of rs2074130 into CC and CT+TT groups. We further investigated the association with clinical symptoms and neural characteristics (brain activation/connectivity and nodal network metrics). ResultsOur results showed significant associations between all selected SNPs and schizophrenia (all P < 0.05). In patients, letter fluency and motor speed scores of T allele carriers were significantly higher than the CC group (all P < 0.05). Interestingly, greater brain activity, functional connectivity, and betweenness centrality (BC) in language processing and motor coordination were also observed in the corresponding brain zones in patients with the T allele based on a two-way ANCOVA model. Moreover, a potential positive correlation was found between brain activity/connectivity of these brain regions and verbal fluency and motor speed. ConclusionOur findings suggest that the DOCK4 gene may contribute to the onset of schizophrenia and lead to language processing and motor coordination dysfunction in this patient population from China.

Randomized controlled trial of computerized approach/avoidance training in social anxiety disorder: Neural and symptom outcomes

Social anxiety is associated with diminished automatic approach toward positive social cues that may limit the ability to connect with others. This diminished approach bias may be a modifiable treatment target. We evaluated the effects of an approach avoidance training procedure on positive emotions, social relationship outcomes, clinical symptoms, and neural indices of social approach and reward processing.Forty-five individuals with social anxiety disorder were randomized (parallel 1:1 randomization) to complete computerized Approach Positive training (n = 21) or Balanced training(n = 24). Sessions included a standardized social interaction task. Participants were blind to training group. Participants completed clinical outcome measures and functional magnetic resonance imaging at baseline and post intervention with an MRI-compatible AAT and the social incentive delay task (SID).Both groups displayed significant improvements of similar magnitude on the primary outcome of social connectedness (between group post-treatment d = −0.21) but not positive affect (d = −0.09), from before to after treatment, persisting through follow-up. Groups demonstrated significant improvements on additional outcomes including anxiety, depression, and anhedonia symptoms. Participants in Approach Positive AAT demonstrated increased activation in the thalamus and medial prefrontal cortex during social versus neutral- approach relative to Balanced AAT during the fMRI AAT. Participants in Balanced AAT showed increased activation in regions within an a priori-defined striatum region of interest mask during anticipation of social reward (vs. baseline) in the SID relative to Approach Positive AAT.At a neural processing level AAT may influence the valuation and motivations associated with positive social cues regulated by the mPFC and thalamus. NCT02136212, NIMH R00MH090243.

Aberrant static and dynamic functional network connectivity in heart failure with preserved ejection fraction.

AimsHeart failure may lead to brain functional alterations related to cognitive impairment. This study aimed to detect alterations of static functional network connectivity (FNC) and dynamic FNC in heart failure with preserved ejection fraction (HFpEF) and to estimate the association between the altered FNC and clinical features related to HFpEF.Methods and resultsThe clinical and resting‐state functional magnetic resonance imaging (fMRI) data of HFpEF patients (n = 35) and healthy controls (HCs) (n = 35) were acquired at baseline. Resting‐state networks (RSNs) were established based on independent component analysis (ICA) and FNC analyses were performed. The associations between the FNC abnormalities and clinical features related to HFpEF were analysed. Compared with HCs, HFpEF patients showed decreased functional connectivity within the default mode network, left frontoparietal network, and right frontoparietal network and increased functional connectivity within the right frontoparietal network and visual network. Negative correlations were observed between decreased dynamic FNC and the left ventricular end‐diastolic diameter (LVDd) (r = −0.435, P = 0.015) as well as the left ventricular end‐systolic diameter (LVDs) (r = −0.443, P = 0.013).ConclusionsThe FNC disruption and altered temporal properties of functional dynamics in HFpEF patients may reflect the neural mechanisms of brain injury after HFpEF, which may deepen our understanding of the disease.

Distinct Gene Expression Profile in Patients With Poor Postoperative Outcomes After Rotator Cuff Repair: A Case-Control Study

Background: Impaired healing after rotator cuff repair is a major concern, with retear rates as high as 94%. A method to predict whether patients are likely to experience poor surgical outcomes would change clinical practice. While various patient factors, such as age and tear size, have been linked to poor functional outcomes, it is currently very challenging to predict outcomes before surgery. Purpose: To evaluate gene expression differences in tissue collected during surgery between patients who ultimately went on to have good outcomes and those who experienced a retear, in an effort to determine if surgical outcomes can be predicted. Study Design: Case-control study; Level of evidence, 3. Methods: Rotator cuff tissue was collected at the time of surgery from 140 patients. Patients were tracked for a minimum of 6 months to identify those with good or poor outcomes, using clinical functional scores and follow-up magnetic resonance imaging to confirm failure to heal or retear. Gene expression differences between 8 patients with poor outcomes and 28 patients with good outcomes were assessed using a multiplex gene expression analysis via NanoString and a custom-curated panel of 145 genes related to various stages of rotator cuff healing. Results: Although significant differences in the expression of individual genes were not observed, gene set enrichment analysis highlighted major differences in gene sets. Patients who had poor healing outcomes showed greater expression of gene sets related to extracellular matrix production (P < .0001) and cellular biosynthetic pathways (P < .001), while patients who had good healing outcomes showed greater expression of genes associated with the proinflammatory (M1) macrophage phenotype (P < .05). Conclusion: These results suggest that a more proinflammatory, fibrotic environment before repair may play a role in poor healing outcome. With validation in a larger cohort, these results may ultimately lead to diagnostic methods to preoperatively predict those at risk for poor surgical outcomes.

Cortico‐subcortical functional connectivity modifications in fatigued multiple sclerosis patients treated with fampridine and amantadine

Fatigue in multiple sclerosis (MS) is common and disabling; medication efficacy is still not fully proven. The aim of this study was to investigate 4-week modifications of fatigue severity in 45 relapsing-remitting MS patients after different symptomatic treatments, and changes in concomitant resting state (RS) functional connectivity (FC). Patients were randomly, blindly assigned to treatment with fampridine (n=15), amantadine (n=15) or placebo (n=15), and underwent clinical assessment and 3-Tesla RS functional magnetic resonance imaging at baseline (t0) and after 4weeks (w4) of treatment. Fifteen healthy controls (HCs) were also studied. Changes in modified fatigue impact scale (MFIS) score and network RS FC were assessed. In MS, abnormalities of network RS FC at t0 did not differ between treatment groups and correlated with fatigue severity. At w4, global scores and subscores on the MFIS decreased in all groups, with no time-by-treatment interaction. At w4, all patient groups had changes in RS FC in several networks, with significant time-by-treatment interactions in basal ganglia, sensorimotor and default-mode networks in fampridine-treated patients versus the other groups, and in frontoparietal network in amantadine-treated patients. In the fampridine group, RS FC changes correlated with concurrently decreased MFIS score (r range=-0.75 to 0.74, p range=0.003-0.05). Fatigue improved in all MS groups, independently of treatment. Concomitant RS FC modifications were located in sensorimotor, inferior frontal and subcortical regions for fampridine- and amantadine-treated patients, and in associative sensory cortices for placebo-treated patients.

Virtual Reality-Based Psychotherapy in Social Anxiety Disorder: fMRI Study Using a Self-Referential Task.

BackgroundAlthough it has been well demonstrated that the efficacy of virtual reality therapy for social anxiety disorder is comparable to that of traditional cognitive behavioral therapy, little is known about the effect of virtual reality on pathological self-referential processes in individuals with social anxiety disorder.ObjectiveWe aimed to determine changes in self-referential processing and their neural mechanisms following virtual reality treatment.MethodsWe recruited participants with and without a primary diagnosis of social anxiety disorder to undergo clinical assessments (Social Phobia Scale and Post-Event Rumination Scale) and functional magnetic resonance imaging (fMRI) scans. Participants with social anxiety disorder received virtual reality–based exposure treatment for 6 sessions starting immediately after baseline testing. After the sixth session, participants with social anxiety disorder completed follow-up scans during which they were asked to judge whether a series of words (positive, negative, neutral) was relevant to them.ResultsOf 25 individuals with social anxiety disorder who participated in the study, 21 completed the sessions and follow-up; 22 control individuals also participated. There were no significant differences in age (P=.36), sex (P=.71), or handedness (P=.51) between the groups. Whole-brain analysis revealed that participants in the social anxiety disorder group had increased neural responses during positive self-referential processing in the medial temporal and frontal cortexes compared with those in the control group. Participants in the social anxiety disorder group also showed increased left insular activation and decreased right middle frontal gyrus activation during negative self-referential processing. After undergoing virtual reality–based therapy, overall symptoms of the participants with social anxiety disorder were reduced, and these participants exhibited greater activity in a brain regions responsible for self-referential and autobiographical memory processes while viewing positive words during postintervention fMRI scans. Interestingly, the greater the blood oxygen level dependent changes related to positive self-referential processing, the lower the tendency to ruminate on the negative events and the lower the social anxiety following the virtual reality session. Compared with that at baseline, higher activation was also found within broad somatosensory areas in individuals with social anxiety disorder during negative self-referential processing following virtual reality therapy.ConclusionsThese fMRI findings might reflect the enhanced physiological and cognitive processing in individuals with social anxiety disorder in response to self-referential information. They also provide neural evidence of the effect of virtual reality exposure therapy on social anxiety and self-derogation.

Multivariate Analysis of Structural and Functional Neuroimaging Can Inform Psychiatric Differential Diagnosis.

Traditional psychiatric diagnosis has been overly reliant on either self-reported measures (introspection) or clinical rating scales (interviews). This produced the so-called explanatory gap with the bio-medical disciplines, such as neuroscience, which are supposed to deliver biological explanations of disease. In that context the neuro-biological and clinical assessment in psychiatry remained discrepant and incommensurable under conventional statistical frameworks. The emerging field of translational neuroimaging attempted to bridge the explanatory gap by means of simultaneous application of clinical assessment tools and functional magnetic resonance imaging, which also turned out to be problematic when analyzed with standard statistical methods. In order to overcome this problem our group designed a novel machine learning technique, multivariate linear method (MLM) which can capture convergent data from voxel-based morphometry, functional resting state and task-related neuroimaging and the relevant clinical measures. In this paper we report results from convergent cross-validation of biological signatures of disease in a sample of patients with schizophrenia as compared to depression. Our model provides evidence that the combination of the neuroimaging and clinical data in MLM analysis can inform the differential diagnosis in terms of incremental validity.

The impact of torture on interpersonal threat and reward neurocircuitry

Torture adversely influences emotional functioning, but the neurophysiological mechanisms underpinning its impact are unknown. This study examined how torture exposure affects the neural substrates of interpersonal threat and reward processing. Male refugees with (N = 31) and without (N = 27) torture exposure completed a clinical interview and functional magnetic resonance imaging scan where they viewed fear, happy and neutral faces. Between-group activations and neural coupling were examined as moderated by posttraumatic stress disorder symptom severity and cumulative trauma load. Posttraumatic stress disorder symptom severity and trauma load significantly moderated group differences in brain activation and connectivity patterns. Torture survivors deactivated the ventral striatum during happy processing compared to non-torture survivor controls as a function of increased posttraumatic stress disorder symptom severity - particularly avoidance symptoms. The ventral striatum was more strongly coupled with the inferior frontal gyrus in torture survivors. Torture survivors also showed left hippocampal deactivation to both fear and happy faces, moderated by trauma load, compared to controls. Stronger coupling between the hippocampus and frontal, temporoparietal and subcortical regions during fear processing was observed, with pathways being predicted by avoidance and hyperarousal symptoms. Torture exposure was associated with distinct brain activity and connectivity patterns during threat and reward processing, dependent on trauma exposure and posttraumatic stress disorder symptom severity. Torture appears to affect emotional brain functioning, and findings have the potential to guide more targeted interventions for torture survivors.

Neural effects of a short-term virtual reality self-training program to reduce social anxiety.

Social anxiety disorder (SAD) is characterized by anxiety regarding social situations, avoidance of external social stimuli, and negative self-beliefs. Virtual reality self-training (VRS) at home may be a good interim modality for reducing social fears before formal treatment. This study aimed to find neurobiological evidence for the therapeutic effect of VRS. Fifty-two patients with SAD were randomly assigned to a VRS or waiting list (WL) group. The VRS group received an eight-session VRS program for 2 weeks, whereas the WL group received no intervention. Clinical assessments and functional magnetic resonance imaging scanning with the distress and speech evaluation tasks were repeatedly performed at baseline and after 3 weeks. The post-VRS assessment showed significantly decreased anxiety and avoidance scores, distress index, and negative evaluation index for 'self', but no change in the negative evaluation index for 'other'. Patients showed significant responses to the distress task in various regions, including both sides of the prefrontal regions, occipital regions, insula, and thalamus, and to the speech evaluation task in the bilateral anterior cingulate cortex. Among these, significant neuronal changes after VRS were observed only in the right lingual gyrus and left thalamus. VRS-induced improvements in the ability to pay attention to social stimuli without avoidance and even positively modulate emotional cues are based on functional changes in the visual cortices and thalamus. Based on these short-term neuronal changes, VRS can be a first intervention option for individuals with SAD who avoid society or are reluctant to receive formal treatment.

A-189 Exploring the Effects of EEG Neurofeedback Training on Verbal Episodic Memory in a TBI Sample

Abstract Objective Traumatic brain injuries (TBI) are commonly characterized by neural changes that impair physical, behavioral, and cognitive functioning across diverse ages and demographics. Cognitive complaints frequently include memory difficulties, with deficits in episodic memory greatly impairing daily functioning and future planning. Although various interventions and rehabilitation techniques have been implemented for TBI, limited treatment options are available for TBI-driven memory complaints. Recent research has explored the use of neurofeedback training (NFT) to improve cognitive functioning in TBI patients, yet it remains unclear whether this intervention may be successful in improving these memory deficits. Method In this double-blind, placebo-controlled pilot study, the use of EEG neurofeedback training (NFT) on verbal episodic memory was explored in 12 veterans with TBI. Participants were randomized to active treatment or sham treatment, and they completed 20 sessions of NFT. Clinical assessments and functional magnetic resonance imaging (fMRI) data were collected pre and post treatment to measure any changes in resting-state functional connectivity or cognitive functioning. Results Findings suggest that immediate recall scores improved following active NFT, as measured by the California Verbal Learning Task-II. We also observed increased resting-state functional connectivity between the ventromedial prefrontal cortex and the inferior temporal lobe following NFT (Fig. 1), which may represent an underlying mechanism of memory improvement. Conclusions These exploratory findings may hold promise for future research on the use of NFT for memory enhancement in various populations.

Resting-state neural network disturbances that underpin the emergence of emotional symptoms in adolescent girls: resting-state fMRI study.

Subsyndromal emotional symptoms in adolescence may represent precursors for full-blown emotional disorders in early adulthood. Understanding the neurobiological mechanisms that drive this development is essential for prevention. Self-referential processing and emotion regulation are remodelled substantively during adolescence, therefore this study examined integration of key neural networks involved in these processes. At baseline, clinical and resting-state functional magnetic resonance imaging data were collected for 88 adolescent girls (mean age 15 years), and 71 of these girls underwent repeat clinical assessment after 2 years. These 71 girls were then partitioned into two groups depending on the presence (ES+) or absence (ES-) of emotional symptoms, and differences in dynamic functional network connectivity were determined and correlated with clinical variables. The two groups displayed a differential pattern of functional connectivity involving the left lateral prefrontal network (LPFN). Specifically, in the ES+ group this network displayed positive coupling with the right LPFN but negative coupling with the default mode network, and the inverse of this pattern was found in the ES- group. Furthermore, the coupling strengths between left and right LPFN at the irst time point predicted follow-up depression and state anxiety scores. Our findings suggest that in adolescent girls, emotional symptoms may emerge as a result of impaired integration between networks involved in self-referential information processing and approach-avoidance behaviours. These impairments can compromise the pursuit of important goals and have an impact on emotion processing and finally may lead to the development of emotional disorders, such as anxiety and depression in adulthood. None.

The Leiden Family Lab study on Social Anxiety Disorder: A multiplex, multigenerational family study on neurocognitive endophenotypes

abstractObjectivesSocial anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so‐called “endophenotypes”. These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety.MethodsThe LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD.ResultsThe sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self‐reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms.ConclusionsBy the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.

Assessing motor, visual and language function using a single 5-minute fMRI paradigm: three birds with one stone.

Clinical functional Magnetic Resonance Imaging (fMRI) requires inferences on localization of major brain functions at the individual subject level. We hypothesized that a single "triple use" task would satisfy sensitivity and reliability requirements for successfully assessing the motor, visual and language domain in this context. This was tested here by the application in a group of healthy adults, assessing sensitivity and reliability at the individual subject level, separately for each domain.Our "triple use" task consisted of 2 conditions (condition 1, assessing motor and visual domain, and condition 2, assessing the language domain), serving mutually as active/control. We included 20 healthy adult subjects. Random effect analyses showed activation in primary motor, visual and language regions, as expected. Less expected regions were activated both for the motor and visual domains. Further, reliability of primary activation patterns was very high across individual subjects, with activation seen in 70-100% of subjects in primary motor, visual, and left-lateralized language regions.These findings suggest the "triple use" task to be reliable at the individual subject's level to assess motor, visual and language domains in the clinical fMRI context. Benefits of such an approach include shortening of acquisition time, simplicity of the task for each domain, and using a visual stimulus. Following establishment of reliability in adults, the task may also be a valuable addition in the pediatric clinical fMRI context, where each of these factors is of high relevance.

Reducing task-based fMRI scanning time using simultaneous multislice echo planar imaging.

To maintain alertness and to remain motionless during scanning represent a substantial challenge for patients/subjects involved in both clinical and research functional magnetic resonance imaging (fMRI) examinations. Therefore, availability and application of new data acquisition protocols allowing the shortening of scan time without compromising the data quality and statistical power are of major importance. Higher order category-selective visual cortical areas were identified individually, and rapid event-related fMRI design was used to compare three different sampling rates (TR = 2000, 1000, and 410ms, using state-of-the-art simultaneous multislice imaging) and four different scanning lengths to match the statistical power of the traditional scanning methods to high sampling-rate design. The results revealed that ~ 4min of the scan time with 1Hz (TR = 1000ms) sampling rate and ~ 2min scanning at ~ 2.5Hz (TR = 410ms) sampling rate provide similar localization sensitivity and selectivity to that obtained with 11-min session at conventional, 0.5Hz (TR = 2000ms) sampling rate. Our findings suggest that task-based fMRI examination of clinical population prone to distress such as presurgical mapping experiments might substantially benefit from the reduced (20-40%) scanning time that can be achieved by the application of simultaneous multislice sequences.

Recovery of Proprioception in the Upper Extremity by Robotic Mirror Therapy: a Clinical Pilot Study for Proof of Concept.

A novel robotic mirror therapy system was recently developed to provide proprioceptive stimulus to the hemiplegic arm during a mirror therapy. Validation of the robotic mirror therapy system was performed to confirm its synchronicity prior to the clinical study. The mean error angle range between the intact arm and the robot was 1.97 to 4.59 degrees. A 56-year-old male who had right middle cerebral artery infarction 11 months ago received the robotic mirror therapy for ten 30-minute sessions during 2 weeks. Clinical evaluation and functional magnetic resonance imaging (fMRI) studies were performed before and after the intervention. At the follow-up evaluation, the thumb finding test score improved from 2 to 1 for eye level and from 3 to 1 for overhead level. The Albert's test score on the left side improved from 6 to 11. Improvements were sustained at 2-month follow-up. The fMRI during the passive motion revealed a considerable increase in brain activity at the lower part of the right superior parietal lobule, suggesting the possibility of proprioception enhancement. The robotic mirror therapy system may serve as a useful treatment method for patients with supratentorial stroke to facilitate recovery of proprioceptive deficit and hemineglect.